In April 1893 he formed a ministry himself, taking as his office that of minister of the interior, but resigned at the end of November, and on 5 December was elected president of the chamber.

He then stood for the presidency, but was defeated, and his cabinet remained in office till January 1895; under this government, Alfred Dreyfus was arrested and condemned (23 December 1894).

The progress of the Dreyfus Affair cast its shadow over Dupuy, along with other French "ministrables," but in November 1898, after Henri Brisson had at last remitted the case to the judgment of the court of cassation, he formed a cabinet of Republican concentration.

In addition, a law passed that same month set out the role of the state-owned Caisse des depots "in the construction and management of subsidised housing".

Although none of Dupuy's presidential bids were successful, he served, due to his position as Prime Minister, as an Acting President of the French Republic for three separate occasions during vacancies.